This invention relates to certain oxadiazolidines, processes for their preparation, their N-oxides, agriculturally suitable salts and compositions, and methods of their use for controlling undesirable vegetation. This invention also relates to mixtures of herbicides that have a synergistic effect on weeds or have a safening effect on crops while retaining or increasing weed control.
The control of undesired vegetation is extremely important in achieving high crop efficiency. Achievement of selective control of the growth of weeds especially in such useful crops as rice, soybean, sugar beet, corn (maize), potato, wheat, barley, tomato and plantation crops, among others, is very desirable. Unchecked weed growth in such useful crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. The control of undesired vegetation in noncrop areas is also important. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different modes of action. Arch. Pharm. (1974), 307, 7-12 discloses the chemical structures of N,N-substituted 4-aryloxazolidindiones. However, it does not disclose the compounds of the present invention.
This invention is directed to compounds and processes to prepare compounds of Formula 1 including all geometric and stereoisomers, N-oxides, and agriculturally suitable salts thereof, agricultural compositions containing them and their use for controlling undesirable vegetation: 
wherein
Q is H; or C1-C12 alkyl, C3-C10 cycloalkyl, C6-C14 bicycloalkyl, C3-C12 alkenyl, C3-C10 cycloalkenyl, C6-C14 bicycloalkenyl or C3-C12 alkynyl, each optionally substituted with one or more R21; or
Q is a 3- to 7-membered fully saturated or 5- to 7-membered partially saturated heterocyclic ring containing one or two X, provided that (a) when X is other than O or S(O)n, then only one X may be present and (b) when two X are present in the ring, they cannot be bonded directly to each other; or
Q is a 5- or 6-membered aromatic heterocyclic ring system containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that the heterocyclic ring system contains no more than one oxygen and no more than one sulfur, and each heterocyclic ring system is optionally substituted with one or more R16; and when Q is a 5- or 6-membered aromatic heterocyclic ring system containing a nitrogen, then Q is bonded through any available carbon or nitrogen atom by replacement of a hydrogen on said carbon or nitrogen atom; or
Q is phenyl optionally substituted with one or more substituents independently selected from the group consisting of R16, phenoxy and Z; or
Q is 
Q is xe2x80x94C(R14)(xe2x95x90NOR15), xe2x80x94C(O)R19, xe2x80x94C(O)OR19, xe2x80x94C(O)SR19, xe2x80x94C(S)R19, xe2x80x94C(S)OR19, xe2x80x94C(S)SR19, xe2x80x94C(O)NR23R24, xe2x80x94C(S)NR23R24, xe2x80x94OR19, xe2x80x94NR19R20, xe2x80x94S(O)nR19 or xe2x80x94S(O)nNR19 R20;
each X is xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94Nxe2x95x90, xe2x80x94NR10xe2x80x94 or xe2x80x94Si(R11)2xe2x80x94;
Y is, together with the carbons to which it is attached, a fully or partially saturated 5-, 6- or 7-membered carbocyclic ring optionally substituted with one or more C1-C4 alkyl groups; or
Y is, together, with the carbons to which it is attached, a fully or partially saturated 5-, 6- or 7-membered heterocyclic ring which contains one or two X and is optionally substituted with one or more R12, provided that when said heterocyclic ring contains two X, then one X is other than O;
Z is phenyl or a 5- or 6-membered aromatic heterocyclic ring system containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that the heterocyclic ring system contains no more than one oxygen and no more than one sulfur, and each phenyl and heterocyclic ring system is optionally substituted with one or more R16;
R1 is C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl or C2-C6 haloalkoxyalkyl; or R1 is C3-C7 cycloalkyl or C3-C7 cycloalkenyl, each optionally substituted with one or more R5; or
R1 is phenyl optionally substituted with one or more R13; or
R1 is a 5- or 6-membered aromatic heterocyclic ring system containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that the heterocyclic ring system contains no more than one oxygen and no more than one sulfur, and each heterocyclic ring system is optionally substituted with one or more R16;
R2 is C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl or NR3R4; or
R2 is 
R1 and R2 are taken together as xe2x80x94CH2 CH2xe2x80x94, xe2x80x94CH2CH2CH2xe2x80x94, xe2x80x94CH2CH2CH2CH2xe2x80x94, xe2x80x94CH2CH2CH2CH2CH2xe2x80x94 or xe2x80x94CH2CH2OCH2CH2xe2x80x94;
R3 is C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl; or
R3 is C3-C7 cycloalkyl or C3-C7 cycloalkenyl, each optionally substituted with one or more R5; or
R3 is a saturated or partially saturated 5-, 6- or 7-membered heterocyclic ring containing 1 to 2 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, and each heterocyclic ring is optionally substituted with one or more R5; or
R3 is phenyl optionally substituted with one or more R26 groups; or
R1 and R3 are taken together with the two nitrogen atoms to which they are attached to form a saturated or partially saturated 5-, 6- or 7-membered heterocyclic ring containing an optional third heteroatom selected from the group consisting of oxygen sulfur and nitrogen, and said heterocyclic ring is optionally substituted with one, or more R9; or
R2 and R13, together with the two atoms to which they are attached and the atom between them, form a fully saturated 5-, 6- or 7-membered carbocyclic or heterocyclic ring containing one oxygen, one sulfur or one or two nitrogen atoms, said heterocyclic ring is optionally substituted with one or more R12, provided that when said heterocyclic ring contains two nitrogen atoms, they are other than bonded directly to each other;
R4 is H or C1-C4 alkyl; or
R3 and R4 are taken together with the nitrogen atom to which they are attached to form a saturated or partially saturated 5-, 6- or 7-membered heterocyclic ring containing an optional second heteroatom selected from the group consisting of oxygen, sulfur and nitrogen, and said heterocyclic ring is optionally substituted with 1-4 R9;
each R5 is independently halogen, C1-C4 alkyl or C1-C4 alkoxy; or when two R5 are attached to the same carbon, then said two R5 groups are taken together as (xe2x95x90O);
each R6 and R7 are independently H or C1-C4 alkyl;
R8 is independently C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy,
each R9 is independently C1-C4 alkyl or C1-C4 alkoxy; or when two R9 are attached to the same carbon, then said two R9 groups are taken together as (xe2x95x90O);
W is, together with the carbons to which it is attached, a fully or partially saturated 5-, 6- or 7-membered heterocyclic ring containing one or two X, provided that (a) when X is other than O or S(O)n, then only one X may be present; (b) when two X are present in the ring, they cannot be bonded directly to each other; and (c) said heterocyclic ring is bonded to the group (CR17R18)q through other than X;
R10 is H, C1-C4 alkyl, C1-C4 haloalkyl, C3-C4 alkenyl, C3-C4 alkynyl, C2-C4 alkoxycarbonyl or C2-C4 alkylcarbonyl; or R10 is phenyl optionally substituted with C1-C3 alkyl, halogen, cyano, nitro or C2-C4 alkoxycarbonyl;
each R11 is C1-C4 alkyl;
each R12 is independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, C1-C4 alkylsufinyl, C1-C4 alkylsufonyl or C2-C4 alkoxycarbonyl;
each R13 is independently halogen, C1-C3 alkyl, Cl-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, C1-C4 alkylthio, C1-C4 haloaIkylthio, C1-C4 alkylsufinyl, C1-C4 alkylsufonyl, cyano, amino, nitro or C2-C4 alkoxycarbonyl;
R14 is H, C1-C6 alkyl, C1-C6 haloalkyl or C2-C6 alkoxyalkyl; or
R14 and R6, together with the carbon atoms to which they are bonded, form a 5- or 6-membered saturated carbocyclic ring optionally substituted with one or more C1-C4 alkyl groups;
R15 is H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C4 alkenyl or C3-C4 alkynyl;
each R16 is independently halogen, nitro, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C3-C4 alkenyl, C3-C4 alkynyl, OR22, NR23R24 or S(O)nR19;
each R17 and R18 are independently H or C1-C4 alkyl;
each R19 and R20 are independently C1-C12 alkyl, C3-C8 cycloalkyl, C3-C12 alkenyl, C3-C8 cycloalkenyl or C3-C12 alkynyl, each optionally substituted with one or more R21;
each R21 is halogen, C4-C8 trialkylsilylalkyl, CN, NO2, xe2x80x94OR22, xe2x80x94NR23 R24, xe2x80x94S(O)nR22, xe2x80x94S(O)nNR23R24, xe2x80x94C(O)R22, xe2x80x94C(S)R22, xe2x80x94C(O)OR22, xe2x80x94C(S)OR22, xe2x80x94C(S)SR22, xe2x80x94C(O)NR23R24, xe2x80x94C(S)NR23R24, xe2x80x94CHR25COR22, xe2x80x94CHR25P(O)(OR22)2, xe2x80x94CHR25P(S)(OR22)2, xe2x80x94CHR25C(O)NR23R24, xe2x80x94CHR25C(O)NH2, xe2x80x94CHR25CO2R22, phenyl optionally substituted with one or more R26 groups or benzyl optionally substituted with one or more R26 groups;
each R22 is C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 alkenyl, C3-C8 alkynyl, C1-C8 haloalkyl, C2-C8 alkoxyalkyl, C2-C8 alkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C4-C8 alkoxyalkoxyalkyl, C4-C8 cycloalkylalkyl, C4-C8 alkenoxyalkyl, C4-C8 alkynyloxyalkyl, C6-C8 cycloalkoxyalkyl, C4-C8 alkenyloxyalkyl, C4-C8 alkynyloxyalkyl, C3-C8 haloalkoxyalkyl, C4-C8 haloalkenoxyalkyl, C4-C8 haloalkynyloxyalkyl, C6-C8 cycloalkylthioalkyl, C4-C8 alkenylthioalkyl, C4-C8 alkynylthioalkyl, C1-C4 alkyl substituted with phenoxy or benzyloxy, each ring optionally substituted with halogen, C1-C3 alkyl or C1-C3 haloalkyl, C4-C8 trialkylsilylalkyl, C3-C8 cyanoalkyl, C3-C8 halocycloalkyl, C3-C8 haloalkenyl, C5-C8 alkoxyalkenyl, C5-C8 haloalkoxyalkenyl, C5-C8 alkylthioalkenyl, C3-C8 haloalkynyl, C5-C8 alkoxyalkynyl, C5-C8 haloalkoxyalkynyl, C5-C8 alkylthioalkynyl, C2-C8 alkyl carbonyl, C2-C8 alkoxy carbonyl, phenyl optionally substituted with halogen, CN, C1-C2 haloalkyl and C1-C2 haloalkoxy or benzyl optionally substituted with halogen, C1-C3 alkyl and C1-C3 haloalkyl;
each R23 is H or C1-C4 alkyl;
each R24 is C1-C4 alkyl or phenyl optionally substituted with one or more R26 groups;
R23 and R24 may be taken together as xe2x80x94(CH2)5xe2x80x94, xe2x80x94(CH2)4xe2x80x94 or xe2x80x94CH2CH2OCH2CH2xe2x80x94, each ring optionally substituted with C1-C3 alkyl, phenyl or benzyl;
each R25 is H or C1-C4 alkyl;
each R26 is C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C2-C5 alkylcarbonyl, C2-C5 alkoxycarbonyl, halogen, amino, cyano or nitro;
R28 is H or C1-C4 alkyl;
X1 and X2 are independently O or S;
X3 is O, S or NR28;
m is 0, 1, 2, 3 or 4;
each n is independently 0, 1 or 2;
p is 0 or 1;
each q is independently 0, 1 or 2; and
t is 0, 1 or 2;
provided that when Q is unsubstituted phenyl, X1, X2 and X3 are O, q is 0 and R2 is methyl, then R1 is other than methyl.
In the above recitations, the term xe2x80x9calkylxe2x80x9dused either alone or in compound words such as xe2x80x9calkylthioxe2x80x9d or xe2x80x9chaloalkylxe2x80x9d includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers. The term xe2x80x9c1-2 alkylxe2x80x9d indicates that one or two of the available positions for that substituent may be alkyl. xe2x80x9cAlkenylxe2x80x9d includes straight-chain or branched alkenes such as 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. xe2x80x9cAlkenylxe2x80x9d also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. xe2x80x9cAlkynylxe2x80x9d includes straight-chain or branched alkynes such as 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. xe2x80x9cAlkynylxe2x80x9d can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl. xe2x80x9cAlkoxyxe2x80x9d includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. xe2x80x9cAlkoxyalkylxe2x80x9d denotes alkoxy substitution on alkyl. Examples of xe2x80x9calkoxyalkylxe2x80x9d include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. xe2x80x9cAlkylthioxe2x80x9d includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. xe2x80x9cCycloalkylxe2x80x9d includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. xe2x80x9cSaturated Carbocyclicxe2x80x9d ring denotes a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.
The term xe2x80x9chalogenxe2x80x9deither alone or in compound words such as xe2x80x9chaloalkylxe2x80x9dincludes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as xe2x80x9chaloalkylxe2x80x9dsaid alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples ofxe2x80x9chaloalkylxe2x80x9d include F3C, ClCH2, CF3CH2 and CF3CCl2. The terms xe2x80x9chaloalkenylxe2x80x9dxe2x80x9chaloalkynylxe2x80x9d, xe2x80x9chaloalkoxyxe2x80x9dand the like, are defined analogously to the term xe2x80x9chaloalkylxe2x80x9d. Examples of xe2x80x9chaloalkenylxe2x80x9d include (Cl)2Cxe2x95x90CHCH2 and CF3CH2CHxe2x95x90CHCH2. Examples of xe2x80x9chaloalkynylxe2x80x9d include HCxe2x89xa1CCHCl, CF3Cxe2x89xa1C, CCl3Cxe2x89xa1C and FCH2Cxe2x89xa1CCH2. Examples of xe2x80x9chaloalkoxyxe2x80x9d include CF3O, CCl3CH2O, HCF2CH2CH2O and CF3CH2O.
The total number of carbon atoms in a substituent group is indicated by the xe2x80x9cCi-Cjxe2x80x9d prefix where i and j are numbers from 1 to 12. For example, C1-C3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, CH3CH(OCH3), CH3OCH2CH2 or CH3CH2OCH2; and C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2 and CH3CH2OCH2CH2. In the above recitations, when a compound of Formula 1 contains a heterocyclic ring, all substituents are attached to this ring through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
When a group contains a substituent which can be hydrogen, for example R3, then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art ,will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. Accordingly, the present invention comprises compounds selected from Formula 1, N-oxides and agriculturally suitable salts thereof The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form.
One skilled in the art will appreciate that not all nitrogen containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form N-oxides. One skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of N-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethydioxirane. These methods for the preparation of N-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed, Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. CR. Katritzky and A. J. Boulton, Eds., Academic Press.
The salts of the compounds of the invention include acid-addition salts with inorganic or organic acids such as hydrobrornic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
Preferred compounds for reasons of better activity and/or ease of synthesis are:
Preferred 1. Compounds of Formula 1 wherein
Q is H; or C1-C12 alkyl, C3-C8 cycloalkyl, C3-C12 alkenyl, C3-C8 cycloalkenyl or C3-C 12 alkynyl, each optionally substituted with one or more R21; or
Q is a 3- to 7-membered fully saturated or 5- to 7-membered partially saturated heterocyclic ring containing one or two X, provided that (a) when X is other than O or S(O)n, then only one X may be present and (b) when two X are present in the ring, they cannot be bonded directly to each other; or
Q is a 5- or 6-membered aromatic heterocyclic ring system containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that the heterocyclic ring system contains no more than one oxygen and no more than one sulfur, and each heterocyclic ring system is optionally substituted with one or more R16; and when Q is a 5- or 6-membered aromatic heterocyclic ring system containing a nitrogen, then Q is bonded through any available carbon or nitrogen atom by replacement of a hydrogen on said carbon or nitrogen atom; or
Q is phenyl optionally substituted with one or more substituents independently selected from the group consisting of R16, phenoxy and Z.
Preferred 2. Compounds of Preferred 1 wherein
Q is C1-C12 alkyl, C3-C8 cycloalkyl, C3-C12 alkenyl, C3-C8 cycloalkenyl or C3-C12 alkynyl, each optionally substituted with one or more R21.
Preferred 3. Compounds of Preferred 1 wherein
Q is a 3- to 7-membered fully saturated or 5- to 7-membered partially saturated heterocyclic ring containing one or two X, provided that (a) when X is other than O or S(O)n, then only one X may be present and (b) when two X are present in the ring, they cannot be bonded directly to each other, or
Q is a 5- or 6-membered aromatic heterocyclic ring system containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that the heterocyclic ring system contains no more than one oxygen and no more than one sulfur, and each heterocyclic ring system is optionally substituted with one or more R16; and when Q is a 5- or 6-membered aromatic heterocyclic ring system containing a nitrogen, then Q is bonded through any available carbon or nitrogen atom by replacement of a hydrogen on said carbon or nitrogen atom.
Preferred 4. Compounds of Preferred 1 wherein
Q is phenyl optionally substituted with one or more substituents independently selected from the group consisting of R16, phenoxy and Z.
Preferred 5. Compounds of Preferred 2 wherein
Q is C1-C6 alkyl optionally substituted with one or more R21, C5-C7 cycloalkyl, C3-C7 alkenyl or C3-C6 alkynyl.
Preferred 6. Compounds of Preferred 3 wherein
Q is a 5- or 6-membered aromatic heterocyclic ring system containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that the heterocyclic ring system contains no more than one oxygen and no more than one sulfur, and each heterocyclic ring system is optionally substituted with one or more R16; and when Q is a 5- or 6-membered aromatic heterocyclic ring system containing a nitrogen, then Q is bonded through any available carbon or nitrogen atom by replacement of a hydrogen on said carbon or nitrogen atom.
Preferred 7. Compounds of Preferred 4 wherein
Q is phenyl optionally substituted with one or more substituents independently selected from the group consisting of R16.
Preferred 8. Compounds of Preferred 2, Preferred 3 or Preferred 4 wherein X1, X2 and X3 are O.
Preferred 9. Compounds of Preferred 7 wherein
Q is phenyl with substituents on the 2-, and 6-position independently selected from the group consisting of R16.
Preferred 10. Compounds of Preferred 5 wherein
q is 0 or 1.
Preferred 11. Compounds of Preferred 6 wherein
q is 0 or 1.
Preferred 12. Compounds of Preferred 7 wherein
q is 0 or 1.
Preferred 13. Compounds of Preferred 1 wherein
R1 is phenyl substituted with one or more R13.
Preferred 14. Compounds of Preferred 1 wherein
R2 is C2-C6 alkyl, C2-C6 haloalkyl or C2-C6 alkoxyalkyl.
Most preferred is the compound of Formula 1 which is selected from the group consisting of:
(a) N-(4-fluorophenyl)-N-(1-methylethyl)-4-(2-methylphenyl)-3,5-dioxo-1,2,4-oxadiazolidine-2-carboxamide;
(b) 4-(2,6-dimethylphenyl)-N-(4-fluorophenyl)-N-(1-methylethyl)-3,5-dioxo1,2,4-oxadiazolidine-2-carboxamiide;
(c) 4-(2,6-dimethylphenyl)N-(1-methylethyl)-3,5-dioxo-N-phenyl-1,2,4-oxadiazolidine-2-carboxamide;
(d) 4-cyclohexyl-N-(1-methylethyl)-3,5-dioxo-N-phenyl-1,2,4-oxadiazolidine-2-carboxamide;
(e) 4-cyclohexyl-N-(4-fluorophenyl)-N-(1-methylethyl)-3,5-dioxo-1,2,4-oxadiazolidine-2-carboxamide
(f) N,4-bis(1-methylethyl)-3,5-dioxo-N-phenyl-1,2,4-oxadiazolidine-2-carboxamiide;
(g) N-(4-fluorophenyl)-N-(1-methylethyl)-3,5-dioxo-4-(cyclopropyl)-1,2,4-oxadiazolidine-2-carboxamide; and
(h) N-(4-fluorophenyl)-N,4-bis(1-methylethyl)-3,5-dioxo-1,2,4-oxadiazolidine-carboxamide.
The oxadiazolidines of Formula 1 are useful as herbicides. The present invention also relates to processes for preparing an oxadiazolidine of Formula 1. The present processes for preparing the oxadiazolidines of Formula 1 provided herein are characterized by employing a process sequence selected from process sequences A, B, C, D or E as described below.
A process for preparing a compound of Formula 1
wherein Q, R6, R7, q, X1, X2, X3, R1 and R2 are as defined above, comprising:
(a) contacting a compound of Formula 5
xe2x80x83wherein R27 is xe2x80x94(CR6R7)qxe2x80x94Q, with a compound of Formula 4
Qxe2x80x94(CR6R7)qxe2x80x94X4xe2x80x83xe2x80x834
xe2x80x83wherein X4 is halogen or mesylate, in the presence of a base to provide a compound of Formula3
(b) contacting the compound of Formula 3 with a carbamoyl or thiocarbamoyl chloride of Formula 2
A process for preparing a compound of Formula 1
wherein Q, R6, R7, q, X1, X2, X3, R1 and R2 are as defined above, comprising:
(a) contacting a compound of Formula 5
xe2x80x83wherein R27 is xe2x80x94(CR6R7)qxe2x80x94Q, with an alcohol of Formula 6
Qxe2x80x94(CR6R7)qxe2x80x94OHxe2x80x83xe2x80x836
xe2x80x83under reaction conditions involving a tertiary phosphine and an azo compound to provide a compound of Formula 3
(b) contacting the compound of Formula 3 with a carbamoyl or thiocarbamoyl chloride of Formula 2
A process for preparing a compound of Formula 1
wherein Q, R6, R7, q, X1, X2, X3, R1 and R2 are as defined above, comprising:
(a) contacting a compound of Formula 5
xe2x80x83wherein R27 is xe2x80x94(CR6R7)qxe2x80x94Q, with a carbamoyl or thiocarbamoyl chloride of Formula 2
xe2x80x83in the presence of a base to provide the compound of Formula 1
xe2x80x83directly or a compound of Formula 7
(b) contacting the compound of Formula 7 with an alcohol of Formula 6
Qxe2x80x94(CR6R7)qxe2x80x94OHxe2x80x83xe2x80x836
xe2x80x83under reaction conditions involving a tertiary phosphine and an azo compound or with a compound of Formula 4
Qxe2x80x94(CR6R7)qxe2x80x94X4xe2x80x83xe2x80x834
xe2x80x83in the presence of a base.
A process for preparing a compound of Formula 1
wherein Q, R6, R7, q, X2, X3, R1 and R2 are as defined above, and X1 is O, comprising:
(a) contacting a compound of Formula 19
xe2x80x83with phosgene or thiophosgene to provide a compound of Formula 20
(b) contacting the compound of Formula 20 with hydroxylamine, following by treatment with a base, and then an acid, to provide a compound of Formula 8
(c) contacting the compound of Formula 8 with a compound of Formula 2
A process for preparing a compound of Formula 1
wherein Q, R6, R7, q, X1, X2, X3, R1 and R2 are as defined above, comprising:
(a) contacting a compound of Formula 2
xe2x80x83with hydroxylamine in the presence of a base to provide a compound of Formula 22
(b) contacting the compound of Formula 22 with a compound of Formula 23
xe2x80x83in the presence of a base to provide a compound of Formula 7
(c) contacting the compound of Formula 7 with an alcohol of Formula 6
Qxe2x80x94(CR6R7)qxe2x80x94OHxe2x80x83xe2x80x836
xe2x80x83under reaction conditions involving a tertiary phosphine and an azo compound or with a compound of Formula 4
Qxe2x80x94(CR6R7)qxe2x80x94X4xe2x80x83xe2x80x834
in the presence of a base.
A process for preparing a compound of Formula 1
wherein Q, R6, R7, q, X1, X2, X3, R1 and R2 are as defined above, comprising contacting a compound of Formula 7
with an orthoformate of Formula 24
(R27O)3CHxe2x80x83xe2x80x8324
wherein R27 is xe2x80x94(CR6R7)qxe2x80x94Q, in the presence of a base.
A process for preparing a compound of Formula 1
wherein Q, R6, R7, q, X1, X2, X3, R1 and R2 are as defined above, comprising:
(a) contacting a compound of Formula 8
xe2x80x83with a compound of Formula 26
xe2x80x83to provide a compound of Formula 25
xe2x80x83or a compound of Formula 27
xe2x80x83in the presence of a catalyst such as hexamethylguanidinium chloride; and
(b) contacting the compound of Formula 25 or Formula 27 with an amine of Formula 13
xe2x80x83in the presence of a base.
The present invention also relates to an intermediate compound of Formula 5
wherein
R27 is xe2x80x94(CR6R7)qxe2x80x94Q; R6, R7, q, Q, X1 and X2 are as defined above for Formula 1;
provided that when X1 and X2 are O and q is 0, then Q is other than unsubstituted benzyl. The present invention also relates to intermediate compounds of Formula 8 and Formula 20
wherein
R6, R7, q, Q and X2 are as defined above for Formula 1; and X1 is O;
provided that when X2 is O and q is 0, then Q is other than unsubstituted benzyl.
The oxadiazolidines of Formula 1 can be used alone or in combination with other commercial pesticides. The present invention also relates to certain rare combinations that surprisingly give greater-than-expected or synergistic effect, or give a less-than-additive or safening effect on crops while retaining or increasing synergistically weed control. The mixtures of compounds of Formula 1 and certain sulfonylureas have now been discovered to synergistically control weeds. Also, the mixtures of compounds of Formula 1 and safeners such as dichlormid or naphthalic anhydride have now been discovered to exhibit a crop safening effect while retaining or synergistically increasing weed control.
This invention also relates to a herbicidal composition comprising a herbicidally effective amount of a compound of Formula 1 and at least one of a surfactant, a solid diluent or a liquid diluent. The preferred compositions of the present invention are those which comprise the above preferred compounds.
This invention also relates to a method for controlling the growth of undesired vegetation comprising contacting the vegetation or its environment with a herbicidally effective amount of a compound of Formula 1.
Compounds of the Formula 1 can be readily prepared by one skilled in the art by using the reactions and techniques described in Scheme 1 to Scheme 10 below. In cases where a substituent of the starting material is not compatible with the reaction conditions described for any of the reaction schemes, the substituent can be converted to a protected form prior to the described reaction scheme and then deprotected after the reaction using commonly accepted protection/deprotection techniques (see Green, T. W and Wuts, P. G., Protecting Groups in Organic Transformations, 2nd Edition, John Wiley and Sons, New York, 1991). Otherwise, alternative approaches known to one skilled in the art are available. The definitions of Q, X1, X2, X3, R1, R2, R6, R7, and q in compounds of Formulae 1-21 below are as defined in the Summary of the Invention.
As shown in Scheme 1, compounds of Formula 1 can be obtained by the reaction of oxadiazolidines of Formula 8 with carbamyl chlorides of Formula 2. The preferred solvent for the carbamoylation reaction is an inert solvent such as tetrahydrofuran, toluene, benzene or dioxane. The presence of a tertiary amine base such as triethylaamine or diisopropylethylarnine is preferable. Use of an acylation catalyst such as 4-dimethylaminopyridine or 4-pyrrolidinopyridine in a catalytic or stoichiometric amount is preferred. Other bases such as alkali hydroxide, carbonates or hydrides may also be employed. The reaction can be carried out at temperatures between 20 to 150xc2x0 C. 
Oxadiazolidines of Formula 8 can be prepared by methods known in the literature. Zinner reported the preparation of a wide variety of oxadiazolidines. See, for example: Arch. Pharm. (1965), 298, 580-587; Arch. Pharm. (1971), 303, 139-144, German patent application, DE 2010396 (1971). As shown in Scheme 2, a hydroxyurea or hydroxythiourea of Formula 9 is reacted with an activated carbonyl or thiocarbonyl compound of Formula 10 in the presence of a base to give compounds of Formula 8. Examples of suitable activated carbonyl compounds are ethyl chloroformate, phenyl chloroformate, carbonyl diimidazole, phosgene, diphosgene or triphosgene. Examples of suitable activated thiocarbonyl compounds are carbon disulfide, thiophosgene and thiocarbonyldiimidazole. Suitable bases include alkali carbonates, tertiary amines such as triethylamine and alkali hydroxides. The reaction can be carried out in a variety of solvents including tetrahydrofuran, toluene, dichloromethane, chloroform, acetonitrile or dioxane. The reaction may also be carried out in two-phase mixtures of water and an organic solvent such as dichloromethane, ethyl acetate or toluene. Depending on the reactivity of the carbonyl or thiocarbonyl compound, the reaction may be carried out at temperatures from 0 to 150xc2x0 C. 
As shown in Scheme 3, compounds of Formula 8a wherein X1 and X2 are O can be made via the method of Zinner, Arch. Pharm. (1981), 314, 294-302. The reaction of isocyanates of Formula 11 with hydroxyurethanes of Formula 12 gives compounds of Formula 8a. The cyclization can be carried out in a variety of solvents such as acetone, dichloromethane, tetrahydrofuran, dioxane, ethyl acetate, and other solvents inert to isocyanates. The presence of a base such as triethylamine or sodium hydroxide is also useful. The reaction may be carried out at temperatures from 20 to 150xc2x0 C. 
Carbamyl chlorides of Formula 2a (which are compounds of Formula 2 wherein X3 is O) are well known in the literature and can be made by the reaction of amines of Formula 13 with phosgene or a phosgene equivalent such as di- or triphosgene as shown in Scheme 4. The presence of a base is useful and the use of hindered tertiary amines such as diisopropylethyl amine is preferred. The reaction can be carried out in a variety of solvents such as toluene or benzene that are inert to phosgene and its equivalents. The reaction can be carried out at temperatures from 0 to 120xc2x0 C. 
As shown in Scheme 5, hydroxyureas and thioureas of Formula 9 can be prepared from the reaction of hydroxylamine with isocyanates or isothiocyanates of Formula 11. The reaction is carried out in a two-phase reaction medium consisting of water and an organic solvent such as toluene, benzene, dichloroethane, dichloromethane, ethyl acetate or chlorobutane. The hydroxylamine employed can be a commercially available aqueous solution or can be prepared in situ from the reaction of an acid addition salt of hydroxylamine with an alkali hydroxide or carbonate. The reaction is generally carried out at temperatures between 0 and 40xc2x0 C. 
Isocyanates of Formula 11a are commercially available or can be prepared from amines of Formula 14 as shown in Scheme 6. The reaction of phosgene or its equivalents (such as di- and triphosgene) with amines or amine hydrochlorides of Formula 14 gives the isocyanates of Formula 11a. This reaction is well known in the literature and can be carried out in a variety of solvents such as toluene, benzene, ethyl acetate or dichloroethane which are inert to phosgene. Depending upon the reactivity of the amine of Formula 14, the reaction may be carried out at temperatures from 0 to 200xc2x0 C. 
As shown in Scheme 7, isocyanates of Formula 11a can also be formed from activated acids of Formula 15. Acid halides, anhydrides, imidazolides and the like can be reacted with various azides to provide, after a Curtius rearrangement, the isocyanates of Formula 11a. The azide used may be an alkali azide, trialkylsilyl azide or trialkylstannyl azide. The reaction may be carried out in solvents such as toluene, tetrahydrofuran, ethyl acetate, dioxane, benzene, or methyl tert-butyl ether. When an alkali azide is employed, biphasic aqueous solvents or miscible aqueous containing mixtures are preferred in the formation of the acyl azide intermediate. For further examples of Curtius rearrangements, see: March, J. Advanced Organic Chemistry, 3rd edition; John Wiley and Sons, 1985; pp 984-985 and 380. See also Kim, World Patent Application 98/51683 (1998) and Larock, Comprehensive Organic Transformations, VCH, 1989, pp 931-932. 
As shown in Scheme 8, compounds of Formula 9 can also be made by the reaction of compounds of Formula 16 with hydroxylamine. The reaction may be carried out in a number of different solvents including tetrahydrofuran, dioxane, acetonitrile, dimethylformamide and dimethylsulfoxide. Temperatures from 0 to 160xc2x0 C. may be employed in this transformation. Many compounds of Formula 16 are known, and can be made by the reaction of commercially available chlorofornates and chlorothioformates with compounds of Formula 14. 
As shown in Scheme 9, compounds of Formula 9 can also be made by the reaction of activated hydroxylamines of Formula 17 with amines of Formula 14. The reaction may be carried out in a number of different solvents including tetrahydrofuran, dioxane, acetonitrile, dimethylformamide and dimethylsulfoxide. In some cases lower alcohols or even mixtures of water and alcohols may also be employed. Temperatures from 0 to 160xc2x0 C. may be employed in this transformation. Compounds of Formula 17 are known in the literature and can be made from hydroxylamine and activated esters or thioesters (See Oesper and Broker, J. Am. Chem. Soc., 1925, 47, 2607; Defoin et. al., Helv. Chim. Acta., 1992, 75, 109-123; and Stewart and Brooks, J. Org. Chem., 1992, 57, 5020-5023). 
Compounds of Formula 2b (which are compounds of Formula 2 wherein X3 is NR23) can be made by the chlorination of ureas of Formula 18 as shown in Scheme 10. The chlorination may be carried out with a wide variety of reagents such as phosphorus oxychloride, thionyl chloride, phosphorous pentachloride, or triphenylphosphine reagents with carbon tetrachloride or chlorine. A variety of solvents may be used including halogenated solvents such as dichloromethane, dichloroethane, or trichloroethane. A preferred solvent of the transformation is dimethylformamide. The reaction may be carried out from 0 to 150xc2x0 C. Some known chloroamidine compounds and their synthesis may be found in Reid, Chem. Ber., 1975, 108, 2290-2299; Kuehle et al.; Angew. Chem.; 1969; 81; 18; and Shevchenko, V. I. et al.; J. Gen. Chem. USSR (Engl.Transl.); 1976;46;535-539. 
Many isothiocyanates of Formula 11a are commercially available. Amines of Formula 13 are commercially available or can be prepared by methods disclosed in the literature. See the following references and references cited therein for synthesis of these materials: Kim, World Patent Application 98/51683 (1998); Dhar, World Patent Application 98/35961 (1998); Rorer, World Patent Application 98/25912 (1998); and Morita et. al., World Patent Application WO 98/11079 (1998).
Amines of Formula 14 are commercially available or can be synthesized by methods known in the art. See the following references and references cited therein for synthesis of these materials: Kim, World Patent Application 98/51683 (1998); Dhar, World Patent Application 98/35961(1998); Rorer, World Patent Application 98/25912 (1998), Goto et. al., European Patent Application EP 695748 (1996); Goto et. al., European Patent Application EP 771,797 (1997); and Goto et. al. U.S. Pat. No. 5,589,439 (1996).
Activated carboxylic acids of Formula 10 are commercially available or can be prepared by methods disclosed in the literature. See the following references and references cited therein for the synthesis of these materials: Kim, World Patent Application 98/51683 (1998); Dhar, World Patent Application 98/35961(1998); Rorer World Patent Application 98/25912 (1998); and Goto et. al., European Patent Application EP 695748.(1996). See also Larock, Comprehensive Organic Transformations, VCH, 1989, p 821 for a list of comprehensive references for the synthesis and chemistry of carboxylic acids and activated derivatives.
This invention is further directed to processes for the preparation of compounds of Formula 1 using process sequences described below.

Step 1 forms compounds of Formula 3 by contacting compounds of Formula 5 with compounds of Formula 4 in the presence of a suitable base either neat or in a suitable solvent.
Compounds of Formula 5 may be prepared, for example, by methods described in Synthesis, 1991, 265.
For Step 1, the reaction temperature is generally from xe2x88x9210 to 250xc2x0 C., preferably from 0 to 100xc2x0 C. The reaction times are generally from 0.25 to 48 h, preferably from 0.25 to 24 h. Generally, the pressure is in the range of 1.013xc3x97102 to 2.026xc3x97102 KPa, preferably ambient pressure. Suitable solvents include typical organic solvents in which the reactants can be dissolved and the process of Step 1 can proceed without interference. Examples of such reactants include aromatics such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, ethers such as dioxane and tetrahydrofuran, nitriles such as acetonitrile and propionitrile, ethyl acetate, dichloromethane, dichloroethane, and polar aprotic solvents such as dimethylformarnide and dimethylsulfoxide.
Suitable bases include organic trialkylamines such as trimethylamine, triethylamine, diisopropylethylamnine, tributylamine and the like, dimethylaniline, N,N-dimethylaminopyridine, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,4-diazabicyclo[2.2.2]octane and 1,5-diazabicyclo[4.3.0]non-5-ene. 1,8-Diazabicyclo[5.4.0]undec-7-ene is a particularly useful organic base for this reaction. Inorganic bases include, but are not limited to, potassium carbonate, sodium carbonate, potassium hydride, sodium hydride, lithium carbonate and cesium carbonate.
A phase transfer catalyst can accelerate the reaction in the presence of inorganic bases. Phase transfer catalysts include tetraalkylammonium halides, crown ethers, phosphonium salts, silicon analogs of crown ethers and acyclic analogs of crown ethers. Particularly useful as a base is the combination of potassium carbonate and a phase transfer catalyst.
Generally at least an equimolar amount of the Formula 4 compound is used in respect to the Formula 5 compound, and preferably at least a small molar excess of the Formula 4 compound is used. More particularly, the molar ratio of the Formula 4 compound to the Formula 5 compound is usually in the range of 1.05:1 to 10:1. In most cases, the molar ratio of the Formula 5 compound to the Formula 4 compound is preferably in the range of 1.1:1 to 1.5:1. Generally at least an equivalent of base is used in respect to the Formula 5 compound, and preferably at least a small equivalent excess of the base is used. More particularly, the ratio of the number of equivalents of base to number of moles of the Formula 5 compound is usually in the range of 1.05:1 to 10:1. In most cases, the ratio of the number of equivalents of base to number of moles of the Formula 5 compound is preferably in the range of 1.1:1 to 1.5:1. The equivalent amount of base may be similar to the molar amount of the Formula 4 compound, but this is not necessary.
The compound of Formula 4 is preferably added to the reaction mixture containing the compound of Formula 5 and a base either neat or in a solvent. The reaction temperature is maintained during and after the addition and until the reaction reaches completion.
Isolation of product of Step 1 can be accomplished by standard workup procedures or the resultant mixture can be used directly in Step 2. 
Step 2 forms compounds of Formula 1 from the reaction of compounds of Formula 3 with compounds of Formula 2 in the presence of a suitable base in a suitable solvent.
For Step 2, the general and preferred reaction conditions are the same as the ones described above for Step 1.
Alternatively, the processes of Step 1 and 2 can be combined without isolating product of Step 1 and preferably, the reaction conditions (e.g. temperature, mole ratio, reaction time etc) are balanced to achieve a high yield of compound of Formula 1.
The compound of Formula 1 can be isolated by standard procedures.

Step 1 forms the compounds of Formula 3 from the reaction of compounds of Formula 5 with compounds of Formula 6 under Mitsunobu reaction conditions involving a tertiary phosphine and an azo compound. One skilled in the art can find a variety of the tertiary phosphine and azo compounds as well as solvents useful for this transformation in Synthesis, 1981, 1 and Org. Reactions, 1992, 42, 335.
For the process of Step 1, the reaction temperature is generally from about xe2x88x9240 to 250xc2x0 C., preferably from xe2x88x9220 to 80xc2x0 C. The reaction times are generally from about 0.20 to 24 h, preferably from 0.5 to 12 h. Generally, the pressure is from 1.013xc3x97102 to 5.065xc3x97102 KPa; preferably ambient pressure.
Generally at least an equimolar amount of the Formula 5 compound is used in respect to the Formula 6 compound, and preferably at least a small molar excess of the Formula 6 compound is used. More particularly, the molar ratio of the Formula 6 compound to the Formula 5 compound is usually in the range of 1.05:1 to 10:1. In most cases, the molar ratio of the Formula 6 compound to the Formula 5 compound is preferably in the range of 1.1:1 to 1.5:1.
Isolation of product of Step 1 can be accomplished by standard workup procedures.
Step 2
Compounds of Formula 1 are then obtained by the reaction of the compounds of Formula 3 prepared in Step 1 and compounds of Formula 2 under the same reaction conditions as already described in Step 2 for Sequence A.

Step 1a forms the compounds of Formula 1 by contacting compounds of Formula 5 with compounds of Formula 2 in the presence of a suitable base either neat or in a suitable solvent.
For the process of Step 1a, the general and preferred reaction conditions are the same as the ones described above for Step 1 in Process Sequence A.
A solution of compound of Formula 2 can be added to a solution/suspension of compound of Formula 5 and a base in a solvent. Reaction temperature is maintained during and after the addition and until the reaction reaches completion. Isolation of product of Step 1a can be accomplished by standard workup procedures. 
Step 1b forms the compounds of Formula 7 from the reaction of compounds of Formula 5 and compounds of Formula 2 in the presence of a base either neat or in a suitable solvent.
For the process of Step 1b, the general and preferred reaction conditions are the same as the ones described above for Step 1 in Process Sequence A.
The product of Step 1b can be isolated by standard workup procedures. 
Step 2a forms the compounds of Formula 1 from the reaction of compounds of Formula 7 and compounds of Formula 6 under Mitsunobu reaction conditions involving a tertiary phosphine and an azo compound. One skilled in the art can find a variety of the tertiary phosphine and azo compounds as well as solvents useful for this transformation in Synthesis, 1981, 1 and Org. Reactions, 1992, 42, 335.
For the process of Step 2a, the reaction temperature is generally from about xe2x88x9240 to 250xc2x0 C., preferably from xe2x88x9220 to 80xc2x0 C. The reaction times are generally from about 0.20 to 24 h, preferably from 0.5 to 12 h. Generally, the pressure is from 1.013xc3x97102 to 5.065xc3x97102 KPa; preferably ambient pressure.
Generally at least an equimolar amount of the Formula 7 compound is used in respect to the Formula 6 compound, and preferably at least a small molar excess of the Formula 6 compound is used. More particularly, the molar ratio of the Formula 6 compound to the Formula 7 compound is usually in the range of 1.05:1 to 10:1. In most cases, the molar ratio of the Formula 7 compound to the Formula 6 compound is preferably in the range of 1.1:1 to 1.5:1.
Isolation of product of Step 2a can be accomplished by standard workup procedures. 
Step 2b forms compounds of Formula 1 by contacting compounds of Formula 7 with compounds of Formula 4 in the presence of a suitable base either neat or in a suitable solvent.
For the process of Step 2b, the general and preferred reaction conditions are similar to the ones described above for Step 1 in Process Sequence A.
Isolation of product of Step 2b can be accomplished by standard workup procedures.
Compounds of the Formula 8 can be readily prepared by one skilled in the art by using the reactions and techniques described in Steps 1 and 2. In cases where a substituent of the starting material is not compatible with the reaction conditions described for any of the reaction schemes, the substituent can be converted to a protected form prior to the described reaction scheme and then deprotected after the reaction using commonly accepted protection/deprotection techniques (see Green, T. W. and Wuts, P. G., Protecting Groups in Organic Transformations, 2nd Edition, John Wiley and Sons, New York, 1991). Otherwise, alternative approaches known to one skilled in the art are available. 
Step 1 forms compounds of Formula 20 from the reaction of compounds of Formula 19 with phosgene or thiophosgene in the presence of a base. For general reaction conditions for this transformation, see: U.S. Pat. No. 5,602,251. Compounds of Formula 19 are well known in the literature. See: for example, J. Chem. Soc. Perkin I (1997), 1041. 
Step 2 forms compounds of Formula 8 in the form of a salt by treatment of compounds of Formula 20 with hydroxylamine and a base. The salt is then converted to compound of Formula 8 by treatment with an acid.
The reaction is conducted in a suitable organic solvent such as, but not limited to, tetrahydrofuran, dioxane or toluene at a temperature between xe2x88x9220 and 100xc2x0 C. with 10-50xc2x0 C. being the preferred temperature. Hydroxylamine may be generated from one of its salts by use of a suitable base such as, but not limited to, potassium carbonate, potassium hydroxide or sodium hydroxide. Alternatively, hydroxylamine in water may be used. Judicious use of an appropriate co-solvent such as water or a phase transfer catalyst may be effective in facilitating the reaction. Further amounts of the base (vide supra) can be added to scavenge the HCl formed in the reaction. Alternatively, an excess amount of hydroxylaniine can be used to achieve the same purpose.
The intermediate compound of Formula 21 is not usually isolated, but converted directly to compounds of Formula 8 by addition of further quantities of base. It is apparent to one skilled in the art that salts of compounds of Formula 8 generated from this reaction may be used directly in the preparation of compounds of Formula 1 as described in Scheme 1. To facilitate the transformation, it may be desirable to adjust the solvent composition by removal of co-solvents such as water prior to the reaction. Alternatively, compounds of Formula 8 may be isolated from their salts by addition of an appropriate mineral acid such as, but not limited to, HCl before being subjected to the reaction conditions as described in Scheme 1 to produce compounds of Formula 1.
Compounds of the Formula 7 can be readily prepared by one skilled in the art by using the reactions and techniques described in Steps 1 and 2. Since hydroxylamine is unstable upon heating, this sequence allows a safe and efficient route to the compounds of the Formula 7 under mild conditions. 
Step 1 forms the compounds of Formula 22 by contacting a compound of Formula 2 with hydroxylamine in the presence of a suitable base in a suitable solvent. Hydroxylamine may be generated from one of its salts or hydroxylamine in water may be used.
For Step 1, the reaction temperature is generally from xe2x88x9210 to 150xc2x0 C., preferably from 0 to 100xc2x0 C. The reaction times are generally from 0.10 to 24 h, preferably from 0.10 to 2 h. Generally, the pressure is in the range of 1.013xc3x97102 to 2.026xc3x97102 KPa; preferably ambient pressure. Suitable solvents include typical organic solvents in which the reactants can be dissolved and the process of Step 1 can proceed without interference. Examples of such solvents include aromatics such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, ethers such as dioxane and tetrahydrofuran, nitriles such as acetonitrile and propionitrile, ethyl acetate, dichloromethane, dichloroethane, and polar aprotic solvents such as dimethylformamide and dimethylsulfoxide. Judicious use of an appropriate co-solvent such as water or a phase transfer catalyst may be effective in facilitating the reaction.
Suitable bases include organic trialkylamines such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine and the like, dimethylaniline, N,N-dimethylaminopyridine, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,4 diazabicyclo[2.2.2]octane and 1,5-diazabicyclo[4.3.0]non-5-ene. Trialkylamines is a particularly useful organic base for this reaction. When an excess quantity of hydroxylamine is employed, the excess hydroxylamine can also serve as a base. Inorganic bases include, but are not limited to, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, lithium carbonate and cesium carbonate.
Generally at least an equimolar amount of the Formula 2 compound is used in respect to hydroxylamine, and preferably at least a small molar excess of hydroxylamine is used. More particularly, the molar ratio of the Formula 2 compound to hydroxylamine is usually in the range of 1:1.05 to 1:10. In most cases, the molar ratio of the Formula 2 compound to hydroxylamine is preferably in the range of 1:1.1 to 1:1.5. Generally at least an equivalent of base is used in respect to the Formula 2 compound, and preferably at least a small equivalent excess of the base is used. More particularly, the ratio of the number of equivalents of base to number of moles of the Formula 2 compound is usually in the range of 1.05:1 to 10:1. In most cases, the ratio of the number of equivalents of base to number of moles of the Formula 2 compound is preferably in the range of 1.1:1 to 1.5:1. The equivalent amount of base may be similar to the molar amount of the Formula 2 compound, but this is not necessary.
Isolation of product of Step 1 can be accomplished by standard workup procedures. In the scenario that the reaction is carried our in an aqueous solution, a filtration can be employed to collect compounds of Formula 22. 
Compounds of Formula 7 are synthesized by contacting compounds of Formula 22 with chlorocarbonyl isocyanate (X1 and X2 are O) or chlorocarbonyl isothiocyanate (X1 is O and X2 is S) or chlorothiocarbonyl isocyanate (X1 is S and X2 is O) or chlorothiocarbonyl isothiocyanate (X1 and X2 are S) in the presence of a base to scavange the HCl byproduct. Similar examples of such reactions using N-alkyl-N-hydroxylamine and chlorocarbonyl isocyanate have been reported in Syn., 1982, 781-2 and in WO 9741097 but there is no example of compound like 22 and chlorocarbonyl isocyanate in the literature.
Compounds of Formula 23 are either commercially available or may be prepared by one skilled in the art using methods known in the art (or slight modification of these methods); for example, see: Chem. Ber. 1981, 114, 1746-51, Chem. Ber. 1973, 106, 1487-95, and Chem. Ber. 1966, 99,3572-81.
For Step 2, the reaction temperature is generally from xe2x88x9210 to 150xc2x0 C., preferably from 0 to 100xc2x0 C. The reaction times are generally from 0.10 to 24 h, preferably from 0.10 to 2 h. Generally, the pressure is in the range of 1.013xc3x97102 to 2.026xc3x97102 KPa; preferably ambient pressure. Suitable solvents include typical organic solvents in which the reactants can be dissolved and the process of Step 1 can proceed without interference. Examples of such reactants include aromatics such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, ethers such as dioxane and tetrahydrofuran, nitriles such as acetonitrile and propionitrile, ethyl acetate, dichloromethane, dichloroethane, and polar aprotic solvents such as dimethylformamide and dimethylsulfoxide.
Suitable bases for Step 2 are similar to the ones described above for Step 1.
Generally at least an equimolar amount of the Formula 22 compound is used in respect to the Formula 23 compound, and preferably at least a small molar excess of the Formula 23 compound is used. More particularly, the molar ratio of the Formula 22 compound to the Formula 23 compound is usually in the range of 1:1.05 to 1:10. In most cases, the molar ratio of the Formula 22 compound to the Formula 23 compound is preferably in the range of 1:1.1 to 1:1.5. Generally at least an equivalent of base is used in respect to the Formula 22 compound, and preferably at least a small equivalent excess of the base is used. More particularly, the ratio of the number of equivalents of base to number of moles of the Formula 22 compound is usually in the range of 1.05:1 to 10:1. In most cases, the ratio of the number of equivalents of base to number of moles of the Formula 22 compound is preferably in the range of 1.1:1 to 1.5:1. The equivalent amount of base may be similar to the molar amount of the Formula 22 compound, but this is not necessary.
Isolation of product of Step 2 can be accomplished by standard workup procedures.
Compounds 7 can be readily converted into alkali salts when treated with potassium carbonate or sodium carbonate in water. The salts may be useful in alkylation reactions.
Compounds of Formula 1 are then obtained by the reaction of compounds of Formula 7 under the same reaction conditions as already described in Step 2a/2b in Sequence C.
Compounds of the Formula 1 can be readily prepared by one skilled in the art by using the reactions and techniques described in the scheme below. 
The compounds of Formula 1 are formed by contacting a compound of Formula 7 with an orthoformate of Formula 24 either neat or in the presence of a suitable solvent.
The reaction temperature is generally from xe2x88x9210 to 150xc2x0 C., preferably from 0 to 100xc2x0 C. The reaction times are generally from 0.10 to 24 h, preferably from 0.10 to 2 h. Generally, the pressure is in the range of 1.013xc3x97102 to 2.026xc3x97102 KPa; preferably ambient pressure. Suitable solvents include typical organic solvents in which the reactants can be dissolved and the process can proceed without interference. Examples of such reactants include aromatics such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, ethers such as dioxane and tetrahydrofuran, nitriles such as acetonitrile and propionitrile, ethyl acetate, dichloromethane, dichloroethane, and polar aprotic solvents such as dimethylformamide and dimethylsulfoxide.
Generally at least an equimolar amount of the Formula 24 compound is used in respect to the Formula 7 compound, and preferably at least a small molar excess of Formula 24 compound is used. More particularly, the molar ratio of the Formula 7 compound to the Formula 24 compound is usually in the range of 1:1.05 to 1:10. In most cases, the molar ratio of the Formula 7 compound to the Formula 24 compound is preferably in the range of 1:1.1 to 1:1.5.
Compounds of the Formula 1 can be readily prepared by one skilled in the art by using the reactions and techniques described in Steps 1 and 2. 
Step 1 forms the compounds of Formula 25 by contacting a compound of Formula 8 with a compound of Formula 26 either neat or in a suitable solvent.
For Step 1, the reaction temperature is generally from xe2x88x9210 to 150xc2x0 C., preferably from 0 to 100xc2x0 C. The reaction times are generally from 0.10 to 24 h, preferably from 0.10 to 2 h. Generally, the pressure is in the range of 1.013xc3x97102 to 2.026xc3x97102 KPa; preferably ambient pressure. Suitable solvents include typical organic solvents in which the reactants can be dissolved and the process of Step 1 can proceed without interference. Examples of such reactants include aromatics such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, ethers such as dioxane and tetraydrofuran, nitriles such as acetonitrile and propionitrile, ethyl acetate, dichloromethane and dichloroethane.
Generally at least an equimolar amount of the Formula 26 compound is used in respect to the Formula 8 compound, and preferably at least a small molar excess of the Formula 26 compound is used. More particularly, the molar ratio of the Formula 8 compound to the Formula 26 compound is usually in the range of 1:1.05 to 1:10. In most cases, the molar ratio of the Formula 8 compound to the Formula 26 compound is preferably in the range of 1:1.1 to 1:1.5.
In the presence of a catalyst such as hexamethylguanidinium chloride, the reaction of compounds of Formula 8 and compounds of Formula 26 produces compounds of Formula 27. For general and preferred conditions, see Tet. Lett. 1987, 5823-5826.
Isolation of product of Step 1 can be accomplished by standard workup procedures. 
Compounds of Formula 1 are synthesized by contacting compounds of either Formula 25 or Formula 27 with amines of Formula 13 in the presence of a suitable base in a suitable solvent.
For Step 2, the general and preferred reaction conditions are the same as the ones described above for Step 1 in Process Sequence A.
One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula 1.
One skilled in the art will also recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. 1H NMR spectra are reported in ppm downfield from tetramethylsilane; s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, dd=doublet of doublets, dt=doublet of triplets, br s=broad singlet.